November 12, 2013

Leading experts convene and issue a Consensus Panel paper on Hepatitis C; which provides an undeniably clear roadmap for addressing this health disparity. The National Medical Association raises the alarm for African Americans and calls for an aggressive approach.

Silver Spring, MD (PRWEB) November 05, 2013

The National Medical Association (NMA) today released the much anticipated Consensus Panel Paper entitled: Hepatitis C: A Crisis in the African American Community. The NMA is the nation’s largest and oldest association of African American physicians and when faced with the startling facts on the burden of Hepatitis C (HCV) in the African American community; Immediate NMA Past President, Rahn K. Bailey, MD convened experts to make recommendations to address this crisis.

Hepatitis C is a viral disease. “Hepatitis C is more common and results in higher primary liver cancer and death rates due to liver disease in African Americans compared to White Americans. This disparity in morbidity and mortality can be reduced by current HCV treatments which cure infection in 55-60% of African Americans.” To explore the issues that lead to higher rates of disease and poorer outcomes among African Americans, the NMA convened a Consensus Panel. The Consensus Panel was Co-Chaired by two of the nation’s leading hepatologists; Charles Howell, MD, Director of Hepatology Research at the University of Maryland and Andrew Muir, MD, Director of Gastroenterology and Hepatology Research at Duke Clinical Research Institute.

The Rationale: The Centers for Disease Control (CDC) recommends that all U.S. baby boomers should get a one-time test for HCV. One in 30 baby boomers – the generation born from 1945 through 1965 – has been infected with HCV, and most don’t know it. The panel supports these guidelines but recommends increased screening of HCV; in all at risk populations. Dr. Andrew Muir explains, “Hepatitis C has the potential to devastate the African American community in the next 10 to 20 years. It is a quiet infection until the very late stages, and so it is critical that all patients particularly African Americans patients get screened for HCV before symptoms develop. There are now treatments that can cure HCV and prevent the complications. We have the ability to prevent cirrhosis and liver cancer from HCV, but we first have to find the patients living with this infection.”

Dr. Charles Howell strongly agrees, “It is imperative that we have focused efforts to identify African Americans infected with HCV and that infected people receive adequate healthcare for this deadly disease.” Dr. Michael LeNoir, President of the NMA, states, “The National Medical Association’s Hepatitis C Consensus Paper is just another step in our process to address the impact of Hepatitis C in all communities with an emphasis on minority populations. The NMA is more committed than ever to the implementation of the Hepatitis C action plan. Our organization will step up the effort to educate our communities and our providers about the potential dangers of HCV infection.”

The National Medical Association’s Hepatitis C Consensus Panel’s findings and recommendations include but are not limited to the following:

There is a need for increased HCV awareness. Data reveal that a minimum of 4 million Americans nationwide are HCV infected, 3 million have a chronic HCV infection, yet the majority of those infected are unaware of their condition. The Consensus Panel recommends that current materials be modified to embody greater concordance with African American culture, values and attitudes. Specifically, the panel recommends that new copy, new graphics, and messages be tested through special funding from the U.S. Centers for Disease Control and that new material be developed that resonate more strongly with African Americans.

There is a need to accelerate current efforts to improve accuracy of HCV prevalence and incidence data which could lead to greater numbers of HCV-infected people entering into treatment. The Consensus Panel recommends that its members and key partners engage in a campaign to support one-time screening for baby-boomer cohorts who comprise the majority of those with an HCV infection; and urges constituent organizations to write endorsements to their health plans so that one-time HCV screening for people born between 1945 and 1965 is included as a core service.

There is a need to reduce or eliminate under-diagnosis of HCV. The Consensus Panel recommends that physicians, nurses and other healthcare professionals bring HCV screening out of their offices and into nontraditional settings where high-need populations reside, rather than waiting for these populations to seek treatment. The panel recommends that every physician and/or other healthcare professionals identify and serve as a continuum of care so that those who test positive for HCV can be immediately linked to treatment.

There is a need to provide training on HCV to current and future healthcare providers.

There is a need for greater inclusion of African Americans in clinical trials. The panel recommends that the NMA expand its intensive training using experts that prepare more African American-serving physicians to participate in clinical trials.

There is a need for increased access to care and treatment for HCV-infected people. The Consensus Panel recommends that the NMA support the enrollment of populations at high risk of HCV into an insurance plan under the Affordable Care Act. The Consensus Panel recommends that all providers train at least one person on staff to directly provide benefits establishment and/or link uninsured patients to organizations that engage in benefit establishment. Through this process, Medicaid and/or Medicare-eligible patients can be linked with public insurance.

There is a need to address Hepatitis C in the criminal justice population. The Consensus panel recommendations include: mandatory HCV screening for all people in jails or prison upon entry; a revision of prison and jail intake sheets so that long-time injection drug users, people with HIV/infection, and other very high-risk groups can be identified; mandatory screening of and provision of information to all people incarcerated upon release; an HVC training curriculum specifically targeted toward the criminal justice population; funding to conduct new research, data collection and analyses of HCV screening, care, and treatment in jails and prisons.

There is a need for increased monitoring of outcomes of HCV screening. The Consensus Panel recommends that medical professionals utilize electronic medical records to track and monitor the outcomes of African Americans infected by HCV.

There is a need to analyze and apply new treatment and treatment approaches. The Consensus panel recommends that the sample sizes, data collection reports, and overall research designs on new treatments and treatment approaches be carefully reviewed.

There is a need to address Gender and HCV. The Consensus Panel recommends that more researchers disaggregate their work by gender so that the unique needs of both African American males and females can be characterized.

For more information; contact the National Medical Association and to download a copy of the report, visit http://www.NMAnet.org.

Founded in 1895, the National Medical Association is the nation’s oldest and largest medical association representing the interests of more than 35,000 African American physicians and their patients. The NMA advocates for policies that assure equitable and quality health care for all people. The Consensus Panel was made possible, in part, by an educational grant and/or contribution from AbbVie, Janssen Pharmaceuticals and OraSure Technologies.

A new multi-year partnership has been forged between the University Health Network (UHN) and pharmaceutical company Boehringer Ingelheim which aims to improve care for hepatitis C patients in Ontario.

Hepatitis C is an infectious disease which, if left undiagnosed and untreated, can result in scarring of the liver, liver failure and potentially liver cancer.

According to data gathered by healthcare experts, hepatitis C affects at least 240,000 Canadians, with some estimates as high as 400,000.

The Canadian Liver Foundation estimates that since 2007 approximately 500 people die from hepatitis C-related illnesses in Canada annually.

According to data from 2009, approximately 10,000 to 12,000 new cases of hepatitis C are diagnosed in Canada each year.

It is also estimated that 21 per cent of Canadians (and possibly more) infected with hepatitis C remain undiagnosed.

While hepatitis C can be diagnosed, treated, managed and cured, there is a definite need for more health care professionals with the required specialized expertise to help hepatitis C patients outside large urban areas in Ontario.

With that in mind, the UHN (which includes Toronto General and Toronto Western Hospitals, Princess Margaret Cancer Centre, and Toronto Rehabilitation Institute) has received $600,000 in funding from Boehringer Ingelheim to launch a new program which takes a three-pronged approach in the battle against hepatitis C.

The program, known as Link-C, aims to inspire more healthcare professionals in rural areas to get the necessary training to treat hepatitis C, encourage people to be screened, diagnosed and educated about the symptoms and treatments for the disease, as well as developing an effective screening program for hepatitis C.

Because the liver is a very resilient organ, Woldanski told us, patients can be infected with the virus for up to 20 or 30 years before any symptoms are manifested, making it a "silent epidemic."

Patients will complain of fatigue, aches and pains and jaundice, though these symptoms can of course be indicators of other illnesses, which makes testing for hepatitis C even more important.

People at increased risk for hepatitis C include those who received a blood transfusion in Canada before 1992, undergone surgical procedures in unsterilized conditions outside North America, those who have shared needles or other drug paraphernalia, received tattooing or piercing without professional sterilized instruments (or through using shared ink), any sexual activity that includes contact with blood, or who have shared items such as razors, manicure and pedicure equipment.

Excessive alcohol consumption will also aggravate hepatitis C.

Woldanski said there are approximately over 1800 people in Algoma with the disease, with about 50 newly-diagnosed cases every year in the region.

Nationally, the number of hepatitis cases is expected to double or triple over the next decade.

Woldanski said: "We're going to start to see more people diagnosed because hopefully, with increased awareness, more people will get tested."

"Treatment is out there and we can cure people."

Woldanski said while the new Link-C initiative is designed to help increase the number of healthcare professionals trained in hepatitis C treatment in rural areas, "in the Sault and Algoma region we're very fortunate because the Ministry of Health has granted us (at GHC) a team approach which supports patients and enhances awareness."

"We have an outreach worker, a registered social worker, two registered nurses with myself included and Dr. Bignell who is a Gastroenterologist who's been treating patients with stomach, bowel and liver disease all along."

However, Woldanski is enthusiastic about Link-C.

"We're also very fortunate to have this new connection between the University Health Network and Boehringer Ingelheim through Link-C, because larger hospitals have clinical trials and all the upcoming treatment regimes."

"We had been treating hepatitis C the same for about 13 years, then all of a sudden there has been a new medication in the last year-and-a-half, with more coming."

Despite the learning curve involved with administering the new medications, Woldanski describes this as "an exciting time" in hepatitis C treatment.

"We can connect with doctors at hospitals in larger urban centres through weekly webinars through Link-C."

"The doctors are able to educate us on an ongoing basis on the latest treatment regimes," Woldanski said, whereas before, patients would often have to be referred to specialists in London or Toronto.

Screening for the disease consists of a blood test.

If that initial blood test is positive, then a second, more specialized blood test is required.

Treatment, with medication, lasts 24 to 48 weeks.

If one medication fails to work, another medication is then tried, with the GHC health team always being vigilant of a patient's liver condition.

Anyone who wishes to be tested for hepatitis C may arrange for a blood test through his/her family doctor, while those without a family doctor may go to Algoma Public Health (APH) for testing.

Patients anywhere in the Algoma region may reach the GHC hepatitis C treatment department at 1-888-943-4372 for assistance.

Hepatitis C virus (HCV) infection in more than 170 million chronically infected patients with no developed preventive vaccine is a globally important issue. In addition to expected hepatic manifestations, a number of extrahepatic manifestations, such as mixed cryoglobulinemia, glomerulonephritis, polyarteritis nodosa, rashes, renal disease, neuropathy, and lymphoma, have been reported following HCV infection, which are believed to be influenced by the virus or the host immune response. HCV combination therapy with pegylated interferon and ribavirin might be associated with side effects as well. The association of HCV with special oral conditions has also been reported recurrently; the mechanism of most of which remains unclear. This article reviews the association of HCV infection with some of the oral conditions such as oral health, Sjogren's syndrome, lichen planus and oral cancer.

Hepatitis C virus (HCV), known previously as parenterally transmitted or posttransfusion non-A non-B hepatitis, was first identified and cloned in 1989. It is an enveloped, single-stranded positive-sense RNA virus, having a diameter of about 50 nm and classified as a separate genus (Hepacivirus) within the Flaviviridae family. [1],[2]

After two decades, with more than 170 million chronically infected people worldwide (3% of the world's population), HCV is now considered as a disease of significant global importance. Although HCV incidence is lower than that of hepatitis B virus (HBV) in many parts of the world, the rate of its chronic infection is much higher [3] and its mortality rate is increasing. [4],[5],[6]

Six major genotypes (1-6) of HCV with various geographical distributions have been identified until now. [1],[7]

The routes of transmission are intravenous drug use, nonprotected sexual contact with multiple partners, iatrogenic acquisition (e.g., hemodialysis), accidental exposure such as needlestick injuries, and less frequently vertical transmission from mother to child. However, no obvious route of acquisition can be identified in 30-40% of HCV infections. [8],[9]

The combination therapy with pegylated interferon and ribavirin, focused on achieving a sustained virological response (SVR), is usually accompanied with side effects. [10],[11],[12]

The morbidity from HCV infection is not only a result of the sequelae of cirrhosis, but also to approximately 30 reported extrahepatic manifestations (EHM), such as mixed cryoglobulinemia, glomerulonephritis, polyarteritis nodosa, rashes, renal disease, neuropathy and lymphoma as well. Despite the available reports, association of some of the other disorders with long-term HCV infection remains controversial. [13],[14],[15],[16],[17]

It is believed that HCV EHMs are influenced by the virus itself or the host immune response following HCV infection, the mechanism of most of which remains unclear. [18],[19] The association between HCV infection and some of the oral conditions (oral health, Sjogren's syndrome, lichen planus, and oral cancer) are reviewed in the present article.

Oral Health

Anecdotal evidence strongly indicates that HCV-infected patients are prone to tooth decay; suffer from esteem loss due to poor oral aesthetics; and have difficulty having a healthy diet due to their poor oral health, being attributed to the number of factors such as injecting drug abuse, methadone medication, and poor utilization of dental services. [20],[21] Chronic diseases are believed to increase the risk of developing dental and oral diseases derived from biological mechanisms either directly (e.g. probable increased risk of developing periodontal disease associated with a diabetes-induced inflammatory response) or indirectly (probable increased risk of dental caries in HCV-infected patients by decreased salivary flow due to prescribed medications). [22],[23]

The provision of dental care falls outside the mainstream of medical funding and the costs of dental treatment are often prohibitive. In addition, HCV infected patients, admitted to the government dental clinics, are often placed on extremely long waiting lists. The inaccessibility of dental treatment may also contribute to the reported extensive tooth destruction and subsequent poor oral health. [20],[24]

The results of a study in the United States showed that high levels of dental treatment are needed among HCV-infected patients. [22]Additionally, a marked discrepancy was shown between the oral health of the HCV infected group and the control in another study in Australia. Both groups were eligible for public dental care, confronting similar access problems and difficulties with waiting lists. However the experience of infected subjects was significantly more worse than HCV-noninfected ones. The number of missing teeth was also significantly higher in HCV-infected patients and periodontal health tended to be poorer. [20]

According to the limited data about the oral health status of HCV-infected patients, mainly from the developed countries, oral health treatment seems necessary. More studies should be performed in the developing countries to make better evaluation of the oral health of HCV-infected patients; where equipment is limited and disorder is more prevalent.

Previous reports have also revealed that some dentists prefer not to work on patients with bloodborne infections, [25],[26],[27],[28]highlighting the continued need for educational courses for dentists to change their attitude and behavior toward infected patients. In addition, routine dental examination of infected patients is recommended to prevent common dental and oral disorders within this group.

Sjogren's Syndrome and Salivary Gland Conditions

The first description of Sjogren's syndrome (SS) was by Mikulicz in 1892, who described a 42-year-old man with bilateral enlargement of the parotid and lacrimal glands associated with a small-round-cell infiltrate.[29]

SS is a chronic autoimmune disorder of the exocrine glands with associated lymphocytic infiltrates in the affected glands. Dryness of the mouth and eyes results from the involvement of the salivary and lacrimal glands. [29],[30],[31] The exact etiology of SS is unknown. Besides other possible factors, a viral etiology has been suggested. [32],[33] However, no single infective causative agent has been identified until now. [34]

Several reports have initially suggested an association between HCV and SS following the development of serological tests, [14],[15] which has been supported with more than 250 reported cases of SS-HCV. [35] Garcia-Carrasco et al. reported an HCV prevalence of 14% among the patients with a previously identified primary SS, which was significantly higher than that of the general population (1.2%). [36] The occurrence of a typical autoimmune sialadenitis in HCV-positive patients, similar to that explained in primary SS, suggests that HCV might efficiently be involved in the SS pathogenesis. [35] Up to 75% of HCV-infected individuals have histological evidence or a test abnormality (ie, xerophthalmia detected by Rose Bengal stain, Schirmer test, sialometry) consistent with SS. [18] Up to 80% of HCV-infected individuals may have some salivary or lachrymal abnormalities, frequently represented by histological signs of mild sialadenitis, whereas clinical evidence of dry mouth and dry eyes is often absent (or may be underestimated). [37]

Proposed mechanisms for such a correlation include cross-reactivity between the HCV envelope and host salivary tissue or HCV envelope-mediated immune stimulation against salivary glands. These mechanisms are supported by studies in mice that were transgenic for the HCV E2 envelope protein. [18]

Distinct differences have been reported between HCV-associated SS and primary SS, namely the absence of anti-Ro/SS-A and anti-La/SS-B, ribonucleoprotein, Jo-1, proliferating cell nuclear antigen, or Scl-70. [17],[38] Several studies have assessed the morphologic and immunohistochemical characteristics of sialadenitis in HCV patients. These results indicated that HCV patients had patterns of salivary gland disease similar to those seen in primary SS patients. [39],[40],[41]

SS and HCV infection have similar pathogenic characteristics. These derangements include overproduction of autoantibodies as a result of B-lymphocyte hyperactivity and expansion of CD5+ B cells that are involved in the production of polyreactive autoantibodies and rheumatoid factor. In addition, analysis of three HCV-infected patients demonstrated a predominance of B cells over T cells in the lymphocytic focus and an increased expression of T lymphocytes in the inflammatory infiltrate. [35],[42]

Approximately 12% of all HCV-infected patients receiving Peginterferon/ribavirin therapy develop xerostomia, which in turn increases the risk of symptoms such as dental cavities, nausea, and constipation. A recent Italian study demonstrated that dry mouth occurring during anti-HCV therapy results from a reversible inhibition of salivary gland function that does not appear to be dose dependent and is promptly reversed upon cessation of treatment. [43]

Different mechanisms may participate in the pathogenesis of SS associated with HCV infection. These happen via direct infection and proliferation of HCV in salivary glands, molecular mimicry between HCV and salivary glands, and formation of immune complexes containing HCV. [35],[44] It has also been demonstrated that replication of the virus itself in the salivary gland epithelial cells might result in hyposalivation. [5]

The pathogenic role of HCV infection in SS remains an issue of debate. Part of this may be a result of misdiagnosis or misclassification and due to the lack of well-defined and commonly accepted diagnostic criteria. The San Diego criteria require objective evidence of sicca syndrome plus evidence of systemic autoimmune disease (eg., autoantibodies and a characteristic minor salivary gland histopathology appearance). At the other end of the spectrum, the European criteria do not require the presence of autoantibodies or a positive salivary gland biopsy finding. Thus, the number of patients fulfilling the European criteria is fivefold to tenfold greater than those fulfilling the San Diego criteria. It has been proposed that HCV infection is a criterion to rule out a primary diagnosis of SS, especially if cryoglobulinemia and hypocomplementemia are present and anti-SSA/Ro antibodies are absent. [37],[45],[46]

Lichen Planus

Lichen planus (LP) is a common T-cell-mediated chronic inflammatory disease of the stratified squamous epithelium with unknown etiology. It can affect the oral mucosa, skin, genitalia, hair follicles, nails, esophagus, urinary tract, nasal mucosa, larynx, and even eyes.[19],[47],[48] Clinically, the oral lichen planus (OLP) has six variants: Papular, reticular, plaque-like, atrophic, erosive, and bullous. These features may occur individually or in combination. [49] Oral manifestations of LP may occur in the absence of skin lesions. The erosive form of OLP causes extreme discomfort and may also be premalignant. [15],[50]

The association of LP with viral agents has been of researchers' interest for a while. Accordingly, one of the most frequently reported oral EHM of HCV infection is OLP. [46],[51] The association between HCV and LP was first described in 1990, a year after the discovery of the virus itself. [52] The investigations were all on antibody-based serological examination. Therefore, the probable association between HCV infection and OLP could not be proved initially. [15]

Although the prevalence of LP among HCV-infected patients has been estimated to be about 5%, the prevalence of anti-HCV in LP patients has been estimated to be as high as 38%. A recent study of 1557 LP patients showed a higher HCV prevalence compared with the control group (1.9% and 0.4%, respectively, P < 0.001). Additionally, a multivariate analysis indicated that LP was associated with HCV infection (OR 4.19, 95% CI 2.21; 7.93). [53]

Indeed, based on the geographical association of HCV and LP, the prevalence of HCV infection among OLP patients varies widely between countries, reaching the highest percentage in HCV hyperendemic areas. [54] Accordingly, the results of a recent systematic review and meta-analysis showed that LP may be significantly associated with HCV infection mainly in Mediterranean countries, Japan, and the United States. Such a possible association has been strongly and consistently suggested through other subanalyses and the sensitivity assessments performed on the issue as well. Because HCV can replicate in skin and oral mucosa, and also since HCV-specific T cells have been found in OLP specimens, the virus could be involved in the pathogenesis of a number of OLP cases, probably via an immunological pathway that are still to be defined. [13] Analysis of experimental data strongly suggests that HCV is involved in the pathogenesis of OLP via local induction of an immune response specific for HCV epitopes. [37]

The role of particular HCV genotypes in the pathogenesis of HCV-related OLP is unlikely, given the observation of LP association worldwide with the same genotypes commonly found in patients without LP. However, genotype 1b seems to be associated with LP, and it appears to be uncommon in the United Kingdom. Studies have shown no differences in serum levels or HCV-RNA levels between HCV-infected patients with and without LP. [37]

Some studies have shown that interferon and ribavirin treatment can improve OLP in HCV-infected patients. [16],[38],[55]

Other studies have shown that OLP may develop or worsen after HCV antiviral treatments. [56] Therefore, the use of interferon in patients with HCV and LP should be undertaken with great caution. [17]

HCV-associated hepatic disease may precede LP onset or may be diagnosed together with it. Apparently, there are no significant differences in the histopathological characteristics specific to OLP or in the ratio of T cells and B cells among infiltrating lymphocytes regardless of the presence or absence of HCV infection. [37],[56],[57] However, the proportion of CD8+ T cells in the lamina propria appears to be higher in HCV-related OLP compared with idiopathic OLP. [34]

Recently, a different genetic cytokine background has been reported in OLP patients with and without HCV infection. Indeed, in the idiopathic form of OLP, the increased production of tumor necrosis factor alpha and interferon gamma is the result of genetic dysregulation of the immune response, [33],[37] whereas OLP patients with HCV infection have a Th1 cytokine bias, possibly secondary to an abnormal immune response to the virus. [34]

With regard to previous studies on the association of OLP and HCV, it is possible to identify some analytical inconsistencies: (1) control groups identified without analyzing the age-specific prevalence of anti-HCV positivity; and (2) inadequacy of previous data toward the real prevalence of HCV infection in the general population. [58]

Hence, it seems too soon to reach a definite conclusion. During recent years and following the development of immunoassays for the detection of anti-HCV antibody, there has been a substantial amount of work on the subject, results of which varied widely, ranging from a strong association to a lack of association.

HCV-RNA has been detected both in sera and in oral lesions of patients with OLP; however, no direct pathogenic effect of HCV on the oral mucosa could be demonstrated. Theoretically, epitopic similarities between HCV and keratinocytes could explain the association between LP and HCV, but this could not be demonstrated in any studies. It is believed that this association might be related to the cytotoxic immune responses to the epithelia cells infected with HCV. [32]

However, when HCV infection is present with OLP, some additional factors, which remain unknown, must also be present. Thus, HCV may be a contributory cause but it is neither necessary nor sufficient to cause OLP on its own. Further studies are required to identify the relevant cofactor (s). [15] It is still highly controversial whether OLP can be considered as an extrahepatic manifestation of HCV infection. Clinicians must always keep in mind that OLP may be associated with a systemic disease. [19] Well-designed prospective, especially cohort studies, mainly from countries with low prevalence of HCV infection, are clearly needed.

Oral Cancer

Oral cancer is a major public health problem in many parts of the globe. It accounts for approximately 400,000 new cases of diagnosed cancers annually. Additionally, it is the cause of 200,000 deaths per annum. Epidemiologic studies revealed a wide range of oral cancer prevalence in different parts of the world, the majority of which confirmed an increasing rate, morbidity, and mortality in the past years. [59],[60] Oral squamous cell carcinoma (OSCC) is the most serious and most common oral malignancy accounting for almost 95% of all lesions. [61]

Although there is no evidence to confirm oral cancer as an HCV EHM, there are studies showing that HCV is very likely to be involved in the development of oral cancer. [62],[63] Several studies have been carried out during recent years to better understand the role of HCV in the development of oral cancer and precancerous lesions. [64],[65]

The incidence of HCV infection in Japanese OSCC patients has been reported to be 16.7-24%. They also investigated the prevalence of HCV infection in oral cancer patients with multiple primary cancers (MPCs) as a risk factor in patients with OSCC. Of 327 patients with OSCC, 59 (18.0%) showed MPCs. In the OSCC patients with MPCs, serum HCV antibodies (anti-HCV) and HCV-RNA were detected in more than 36% and 28%, respectively. [66],[67] The same group of investigators reported a patient with chronic hepatitis C, who developed oral cancer. They also detected HCV-RNA in the oral cancer tissues. [62] In a study on the prevalence of hepatitis virus infection in association with oral diseases requiring surgery performed in Japan, Takata et al., found that HCV antibody was higher in patients with oral cancer. However, the authors concluded that increased incidence of HCV antibody apparently was a reflection of age and that HCV infection may not have an etiologically important association with oral cancer. [68]

On the other hand, an uncontrolled study in the United States reported that 21% of 99 patients with head and neck SCC had HCV infection.[69] Other studies also demonstrated that potentially oral premalignant lesions, such as leukoplakia and oral epithelial dysplasia, are not associated with HCV infection. [70],[71],[72]

In a retrospective study on 402 OLP patients, the role of HCV infection on OLP outcome was analyzed. [73] Although 44% of the patients who developed an oral cancer were HCV infected, the risk was not significantly increased, possibly because of the low statistical power. However, HCV is a common cause of liver cirrhosis, which may present itself as an independent risk factor for the development of oral cancer. [34],[74]

It is very important to detect the lesions in patients with oral cancer when they are at a primary stage. All these findings emphasize the importance of periodic examination of the oral cavity among patients with HCV infection. Studies on the role of immunological pathways as well as the mechanism of the development of the disease are recommended.

Conclusion

Based on the published findings, OLP and SS may be significantly associated with HCV infection, and the virus may be involved in the pathogenesis of these diseases, probably via an immunological pathway. OLP association with HCV was found to be influenced by a geographical distribution. The association of other oral conditions with HCV infection, however, needs further investigation. The association between certain chronic diseases and an increased prevalence of dental disease suggests that many systemic diseases have oral manifestations. Thus, dental professionals could be an important resource for screening and referring patients with chronic diseases. A fast, accurate, and relatively inexpensive oral test has been used to diagnose HIV, and a new oral test should be available soon for HCV.

It should also be emphasized that the therapy options of the above-mentioned oral conditions in the presence of HCV infection has been considered the same as noninfected patients in the related manuscripts. Other probable therapy suggestions should be evaluated in case-control studies to clarify this issue.

WASHINGTON, DC — Patients with hepatocellular carcinoma account for an increasing proportion of patients infected with hepatitis C on the waiting list for liver transplantation, a retrospective cohort study has found.

"We feel that primary prevention for hepatocellular carcinoma will be key to reversing this trend," Jennifer Flemming, MD, from Queen's University in Kingston, Ontario, told Medscape Medical News.

"In patients with hepatitis C, viral eradication is the most important step in reducing an individual's risk of developing hepatocellular carcinoma," she explained. "As the landscape of antiviral treatment continues to evolve and become easier from both the patient and clinician perspective, we would hope that increased rates of sustained viral response result in a lower incidence of hepatocellular carcinoma and, subsequently, a decrease in the number of individuals listed."

Dr. Flemming presented the findings here at The Liver Meeting 2013. She began the work as a clinical research fellow at the University of California, San Francisco.

Patients with hepatocellular carcinoma are given an exception to the Model for End-Stage Liver Disease (MELD) score, developed by the United Network for Organ Sharing (UNOS) to prioritize patients in most urgent need of liver transplantation. The MELD score, which ranges from 6 to 40, takes into account bilirubin, prothrombin time, and creatinine. Patients with scores of 16 and above are considered to be transplant candidates. Patients with hepatocellular carcinoma are automatically given extra points.

Dr. Flemming's team examined data from the Scientific Registry of Transplant Recipients, which includes all liver transplant waitlist candidates in the United States.

Of the 20,325 patients with liver disease related to hepatitis C infection (about 30% of the total), the indication for listing was end-stage liver disease for 12,724 patients and hepatocellular carcinoma for 7061. Those listed for hepatocellular carcinoma were older (56 vs 52 years; P < .001) and more likely to be male (79% vs 73%; P < .001) than those listed for end-stage liver disease.

More Hepatocellular Carcinoma

After adjustment for age and sex, the overall rate of patients with hepatitis C rose from 6.9 per 100,00 in 2003 to 10.2 per 100,000 in 2010 (P < .001). This was entirely due to the 12% annual increase in patients with hepatocellular carcinoma; the average annual increase in patients with end-stage liver disease was a nonsignificant 1%.

“The demand for liver transplantation for hepatocellular carcinoma will likely continue to rise.”

"Looking to the future, the demand for liver transplantation for hepatocellular carcinoma will likely continue to rise and further strain the donor pool," Dr. Flemming said. She added that this situation could "push the transplant community to consider nontransplant alternatives for the disease."

The researchers could not account for the plateau in transplant listings for end-stage liver disease in the hepatitis C population, but there are several hypotheses, Dr. Flemming told Medscape Medical News.

The management of patients with cirrhosis in the gastrointestinal and hepatology community could be improving, which might prevent or delay the development of liver decompensation.

"With the publication of clinical guidelines from the American Association for the Study of Liver Diseases [AASLD] on the management of ascites, esophageal varices, portal hypertension, and hepatocellular carcinoma, clinicians may be more educated and feel more comfortable managing complex patients than in the past," Dr. Flemming said.

In addition, increased viral clearance from recently available antiviral therapy for hepatitis C could be reducing the need for liver transplantation, she noted.

Unfair Advantage

There is general agreement within the hepatology community that this exception has become increasingly unfair to non-hepatocellular carcinoma patients with end-stage liver disease, said session moderator Susan Orloff, MD, from Oregon Health & Science University, and chief of the liver transplantation program at the Portland VA Medical Center.

"The issue is that we are overadvantaging patients with hepatocellular carcinoma," she told Medscape Medical News. "Despite the fact that the total number of waitlisted patients with hepatitis C has increased, that increase is solely due to patients with this carcinoma. We have to figure out an allocation system that allows non-hepatocellular carcinoma patients to have equal access to organs," said Dr. Orloff.

There have been attempts within the AASLD and UNOS to come up with a better way of allocating donor livers, she noted.

"We're in the process of trying to sort it out. Should we require a wait time for patients with hepatocellular carcinoma before they can get activated on the list? But how would you choose those patients?"

The key will be to identify genomic biomarkers in tumors that predict the likelihood of progression, Dr. Orloff said.

"I think we have to figure out a scoring system within the hepatocellular carcinoma group to see who has a greater likelihood of progressing, so we don't put them in the hold bucket," she explained. "Those who don't have a high risk of progression could wait 6 or 8 months. But it also depends on individual biology; it's a very difficult situation. There's no hard and fast answer."

DEERFIELD, Ill., Nov 12, 2013 (BUSINESS WIRE) -- Walgreens WAG -0.01% WAG -0.01% recently presented research from two retrospective cohort studies exploring HIV and comorbid medication adherence at HIV-specialized pharmacies and the implications for HIV patients with serious mental illness(1). The research, presented at the Cell-Lancet conference, What Will it Take to Achieve an AIDS-free World?, in San Francisco, demonstrates that adherence to therapeutic treatments for HIV and associated comorbidities, such as serious mental illness, was significantly higher for patients using Walgreens HIV-specialized pharmacies than for patients using other Walgreens retail pharmacies.

"Medication adherence is vital to maintaining optimal health for patients with the HIV virus. Poor medication adherence can lead to treatment failure, resistance to therapy and increased mortality and is one of the greatest and most costly barriers in treating illness today," said Janeen DuChane, PhD, senior director of clinical outcomes and analytics, Walgreens. "By developing specialized patient support programs, we can improve adherence for HIV patients, better serve HIV populations and reduce medical costs."

In examining the differences in medication adherence for patients using Walgreens HIV-specialized pharmacies and those using other Walgreens retail pharmacies, researchers confirmed that HIV patients utilizing the specialized pharmacies were more adherent to their anti-retroviral and comorbid therapies. The study found that the mean proportion of days covered for patients using Walgreens HIV-specialized pharmacies was significantly higher than for patients using other Walgreens retail pharmacies.

-- For patients taking angiotensin converting enzyme or angiotensin receptor blocker (drugs used to treat hypertension), Walgreens HIV-specialized pharmacy users had a significantly higher mean proportion of days covered of 82.6 percent compared with 79.6 percent in patients using other Walgreens retail pharmacies.

-- Among patients taking statins (drugs used to treat high cholesterol), Walgreens HIV-specialized pharmacy users also had a higher mean proportion of days covered of 83.7 percent than those using other Walgreens retail pharmacies (81.3 percent).

In a separate study, Walgreens researchers conducted a retrospective data analysis of HIV patients with serious mental illness, a group that often experience challenges associated with the willingness and ability to take medication as prescribed which can contribute to a two-fold increase in hospitalization costs. Nearly 30 percent of HIV patients assessed had an indication of serious mental illness comorbidity and demonstrated increased medication adherence(2) when utilizing a Walgreens HIV-specialized pharmacy. Specifically, the study found:

-- Among HIV patients with serious mental illness who exclusively used HIV-specialized pharmacies, 32.7 percent were adherent to their anti-retroviral therapy versus 19.4 percent for HIV patients with serious mental illness using other Walgreens retail pharmacies.

Both studies validate the benefit of patient medication adherence associated with HIV-specialized pharmacies and underscore Walgreens commitment to be a part of the solution to end AIDS. Walgreens award-winning HIV-specialized pharmacies provide education, counseling, testing and treatment through its more than 2,000 HIV-trained pharmacists at more than 700 locations.

The Cell-Lancet conference, What Will it Take to Achieve an AIDS-free World?, gathered both research and medical experts to share and discuss the latest developments in the fight against HIV/AIDS.

About Walgreens

As the nation's largest drugstore chain with fiscal 2013 sales of $72 billion, Walgreens (www.walgreens.com) vision is to be the first choice in health and daily living for everyone in America, and beyond. Each day, Walgreens provides more than 6 million customers the most convenient, multichannel access to consumer goods and services and trusted, cost-effective pharmacy, health and wellness services and advice in communities across America. Walgreens scope of pharmacy services includes retail, specialty, infusion, medical facility and mail service, along with respiratory services. These services improve health outcomes and lower costs for payers including employers, managed care organizations, health systems, pharmacy benefit managers and the public sector. The company operates 8,131 drugstores in all 50 states, the District of Columbia, Puerto Rico and the U.S. Virgin Islands. Take Care Health Systems is a Walgreens subsidiary that is the largest and most comprehensive manager of worksite health and wellness centers and in-store convenient care clinics, with more than 750 locations throughout the country.

Two new therapies awaiting FDA approval for the treatment of hepatitis C come with a cure rate as high as 90 percent.

As many as 3.2 million Americans are infected with the hepatitis C virus, and a bevy of new treatments are on the horizon that promise to kill the infection for good.

The U.S. Food and Drug Administration’s (FDA) Antiviral Drugs Advisory Committee recently recommended two new drugs, sofosbuvir and simeprevir, for full approval.

Simeprevir from Johnson & Johnson and sofosbuvir from Gilead Sciences are two new therapies expected to come on the market soon and are being hailed as the first cure for a viral disease. The drugs work by preventing the virus from reproducing in the body.

Unlike current therapies, these new oral medication combinations require only a 12-week course and have a higher rate of success with fewer side effects. The most widely used injectable treatment currently on the market, interferon, has unwanted side effects, including fatigue, nausea, and depression.

A major hurdle in treating hepatitis C is that many people are unaware they have it. The disease rarely shows symptoms early on but can slowly destroy a person’s liver over decades. Often, people with hepatitis C don’t know they’re infected until cirrhosis or liver cancer develops.

The U.S. Centers for Disease Control (CDC) now recommends that all baby boomers, or those born between 1945 and 1965, get tested, because they account for 75 percent of all hepatitis infections in the U.S. They say one-time testing of all baby boomers would discover 800,000 undiagnosed cases, resulting in 120,000 lives saved.

80 to 90 Percent Success Rate

A phase II study found that a combination of sofosbuvir and simeprevir cleared the virus in 90 percent of the 197 participants with hepatitis C. Patients in the study had not responded to interferon, the current standard of treatment, or had advanced liver problems because of the virus.

There were some side effects: during the 12-week treatment course, about 25 percent of patients who were given simeprevir developed a rash, and another five percent developed sunburn.

In a phase III trial for simeprevir, 80 percent of the 393 patients with genotype 1 hepatitis C—which accounts for 70 percent of all hepatitis C cases in the U.S.—were cleared of the virus after 12 weeks of therapy. The drug was administered once daily along with long-acting interferon and ribavirin, another antiviral medication.

NORCROSS, Ga., Nov. 12, 2013 (GLOBE NEWSWIRE) -- Galectin Therapeutics Inc.(Nasdaq:GALT), the leading developer of therapeutics that target galectin proteins to treat fibrosis and cancer, today reported that five of the eight patients have been enrolled and infused in cohort 1 of its blinded Phase 1 clinical trial of GR-MD-02 for patients with nonalcoholic steatohepatitis (NASH or fatty liver disease) with advanced fibrosis. The Company also reported its financial results for the third quarter and first nine months ended September 30, 2013. These results are included in the Company's Quarterly Report on Form 10-Q, which has been filed with theSecurities and Exchange Commission.

"We are pleased to announce completion of enrollment of the first five of eight patients in our Phase 1 clinical trial for patients with NASH (fatty liver disease) with advanced fibrosis. The patients enrolled have not incurred any serious adverse events. Completion of the enrollment of the first cohort will be an important milestone in the development of our proprietary, novel technology and, if all goes as expected, the clinical data from the first cohort should be available early in 2014," said Peter G. Traber, M.D., Chief Executive Officer, President and Chief Medical Officer, Galectin Therapeutics. "This Phase 1 first-in-man study will evaluate the safety, tolerability, pharmacokinetics and exploratory biomarkers for efficacy for single and multiple doses of GR-MD-02 when administered to patients with fatty liver disease with advanced fibrosis."

The Company also is working with Providence Portland Medical Center in planning for a Phase 1 clinical trial to evaluate the combination of Bristol-Myers Squibb's Yervoy® (ipilimumab) and the Company's GR-MD-02 in patients with metastatic melanoma. This trial is based on pre-clinical data obtained in collaboration with Dr. Will Redmond at the center which demonstrated that the combination of immune checkpoint inhibitors like ipilimumab with GR-MD-02 enhances the antitumor effect in syngeneic mouse cancer models.

At September 30, 2013, the Company had $9.7 million of non-restricted cash and cash equivalents available to fund future operations. Subsequent to quarter end, the Company received$1.6 million from the exercise of warrants and options, with $1.5 million coming from warrant exercises by 10X Fund L.P. Additionally since September 30, 2013, the Company received $0.5 million in net proceeds from the issuance of 50,643 shares through its At Market stock issuance program at an average price per share of $10.82. The Company believes that the cash on hand at quarter end and already received is sufficient to fund operations and planned research and development into the third quarter of 2014. The Company routinely evaluates financing alternatives to raise additional funding to support the next steps in its clinical development program, including, from time to time, potentially issuing shares through the At Market stock issuance program.

For the third quarter of 2013, the Company reported a net loss applicable to common stock of$3.7 million, or ($0.22) per share, basic and diluted, compared with a net loss applicable to common stock of $3.0 million or ($0.19) per share for the same period in 2012. The increase in net loss applicable to common stock is primarily due to a $989,000 increase in the non-cash charge related to stock based compensation. Research and development expense for the third quarter of 2013 was $1.2 million, compared with $1.4 million for the same period in 2012. General and administrative expense for the third quarter of 2013 was $2.4 million, compared with$1.5 million for the same period in 2012. The primary reasons for the increase were non-cash stock-based compensation and legal expense offset somewhat by decreased rent expense.

For the nine months ended September 30, 2013, the Company reported a net loss applicable to common stock of $18.8 million, or ($1.15) per share, basic and diluted, compared with a net loss of $8.2 million, or ($0.55) per share for the same period in 2012. The increase in net loss applicable to common stock is primarily due to an $8.8 million or ($0.53) per share one-time, non-cash stock compensation charge recorded in the second quarter of 2013. Research and development expense for the nine months ended September 30, 2012 increased to $4.3 millioncompared with $3.5 million for the same period in 2012, due primarily to clinical program expenses related to the Phase 1 clinical trial. As we continue to enroll patients in the Phase 1 trial, we expect our clinical activities costs may increase and fluctuate from quarter to quarter as the trial progresses. General and administrative expense for the nine months ended September 30, 2013 increased to $5.0 million compared with $4 million for the same period in 2012, due primarily to increases in non-cash stock based compensation and legal expenses related to ongoing litigation with the Company's former CEO and investor relations expenses, offset by decreased rent expense due to our relocation to Georgia in October 2013.

About Galectin Therapeutics

Galectin Therapeutics (Nasdaq:GALT) is developing promising carbohydrate-based therapies for the treatment of fibrotic liver disease and cancer based on the Company's unique understanding of galectin proteins, key mediators of biologic function. We are leveraging extensive scientific and development expertise as well as established relationships with external sources to achieve cost effective and efficient development. We are pursuing a clear development pathway to clinical enhancement and commercialization for our lead compounds in liver fibrosis and cancer. Additional information is available at www.galectintherapeutics.com.

Forward Looking Statements

This press release contains, in addition to historical information, forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements relate to future events or future financial performance, and use words such as "may," "estimate," "could," "expect" and others. They are based on our current expectations and are subject to factors and uncertainties which could cause actual results to differ materially from those described in the statements. These statements include those regarding our plans, expectations and goals regarding the clinical trial, including our expectation that clinical data from the first cohort should be available early in 2014 , the Company's plans regarding a potential Phase 1 clinical trial to evaluate the combination of Bristol-Myers Squibb's Yervoy® (ipilimumab) and the Company's GR-MD-02 in patients with metastatic melanoma, and plans regarding future funding alternatives and the sufficiency of cash on hand to fund future operations and planned research and development into the third quarter of 2014. Factors that could cause our actual performance to differ materially from those discussed in the forward-looking statements include, among others, that our plans, expectations and goals regarding the clinical trial or any future trials are subject to factors beyond our control and there is no guarantee that we will avoid delays in the development of our drug products or receive FDA approval for any of our drugs in development. Our clinical trial and any future trials may not produce positive results in a timely fashion, if at all, and any necessary changes during the course of a trial could prove time consuming and costly. We may have difficulty in enrolling candidates for testing, which would impact our estimates regarding timing, and we may not be able to achieve the desired results. Upon receipt of FDA approval, we may face competition with other drugs and treatments that are currently approved or those that are currently in development, which could have an adverse impact on our ability to achieve revenues from any proposed indications. Plans regarding development, approval and marketing of any of our drugs, including GR-MD-02, are subject to change at any time based on the changing needs of our company as determined by management and regulatory agencies. To date, we have incurred operating losses since our inception, and our ability to successfully develop and market drugs may be impacted by our ability to manage costs and finance our continuing operations. For a discussion of additional factors impacting our business, see our Annual Report on Form 10-K for the year ended December 31, 2012, and our subsequent filings with the SEC. You should not place undue reliance on forward-looking statements. Although subsequent events may cause our views to change, we disclaim any obligation to update forward-looking statements.

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